A considerable research effort has been made to characterize the central effects of the opioids in terms of brain catecholamine neurotransmission. However, the mesocorticolimbic dopamine system, which has neuronal perikarya in the ventral tegmental area and axonal terminals in the nucleus accumbens, has not been studied to a great extent in this regard. The first objective of this proposal is to characterize the effects of opioids on mesocorticolimbic dopamine function. This will be performe by acute microinjection of opioid into the ventral tegmental area or nucleus accumbens of the rat. After microinjection, I will assess effects on the mesocorticolimbic dopamine system by neurochemical measurements of dopamine release, synthesis and turnover, and by behavioral measurements of motor activity. The effects of peripherally administered opioids will then be compared with the effects of intracranially administered opioids. In addition to the opioids, the indirect sympathomimetics, cocaine and amphetamine, have been shown to affect mesocorticolimbic dopamine function. Therefore, a second objective of this proposal is to evaluate an interaction between the opioids and cocaine and amphetamine. Again, microinjection of drugs into the ventral tegmental area or nucleus accumbens, followed by neurochemical and behavioral measurements shall be used to evaluate a potential interaction. Daily administration with amphetamine or cocaine causes a progressive increase in the mesocorticolimic-mediated behavioral and neurohemical effects produced by these drugs. It has also been found that daily injection with opioid into the ventral tegmental area produces a progressive increase in mesocorticolimbic-mediated responses. Thus, as a third objective of this proposal, I will evaluate an interaction between the opioids, amphetamine and cocaine in this behavioral and neurochemical "sensitization" phenomenon. These studies will provide insight into how the opioids affect the mesocorticolimbic dopamine system. It also evaluates an interaction between the acute and chronic administration of the opioids and the commonly abused sympathomimetics, cocaine and amphetamine. Not only have some studies implicated the involvement of the mesocorticolimbic dopamine system in the reinforcing properties of the opioids, cocaine and amphetamine, but the use of these drugs in combination in our society is becoming an increasingly severe social problem.